The following discussion of the prior art is intended to present the invention in an appropriate technical context and allow its significance to be properly appreciated. Unless clearly indicated to the contrary, however, reference to any prior art in this specification should be construed as an admission that such art is widely known or forms part of common general knowledge in the field.
Apremilast is a phosphodiesterase 4 (PDE4) inhibitor. Apremilast is chemically known as N-[2-[(1S)-1-(3-ethoxy-4-methoxyphenyl)-2-(methylsulfonyl)ethyl]-2,3-dihydro-1,3-dioxo-1H-isoindol-4-yl]acetamide having Formula (I).

Apremilast is indicated for the treatment of adult patients with active psoriatic arthritis. It is available under the trade name of OTEZLA® as an inhibitor of phosphodieasterase 4 (PDE4) and OTEZLA tablets are supplied in 10, 20, and 30 mg strengths for oral administration.
U.S. Pat. No. 6,020,358 discloses racemic 2-[1-(3-ethoxy-4-methoxy phenyl)-2-(methylsulfonyl)ethyl]-2,3-dihydro-1,3-dioxo-1H-isoindol-4-yl]acetamide and process for its preparation, which is incorporated herein by reference.
U.S. Pat. No. 7,427,638 discloses stereomerically pure (+)-2-[1-(3-ethoxy-4-methoxyphenyl)-2-methylsulfonylethyl]-4-acetylaminoisoindoline-1,3-dione, substantially free of its (−) isomer, or a pharmaceutically acceptable metabolite, salt, solvate or hydrate, thereof and its pharmaceutical composition. The stereomerically pure (+)-2-[1-(3-ethoxy-4-methoxyphenyl)-2-methylsulfonyl-ethyl]-4-acetylaminoisoindoline-1,3-dione is the (+)-isomer of racemic 2-[1-(3-ethoxy-4-methoxyphenyl)-2-(methylsulfonyl)ethyl]-2,3-dihydro-1,3-dioxo-1H-isoindol-4-yl]acetamide.
WO 2012/097116 and U.S. 2014/0081032 disclose processes for the preparation of isoindoline compounds and their isotopologues including apremilast.
U.S. 2013/0217918 discloses processes for enantioselective preparation of arylmethanesulfonylethylamines using chiral auxiliaries (S)-1-(3-ethoxy-4-methoxyphenyl)-2-methanesulfonylethylamine which is used for the preparation of apremilast.
WO 2009/120167 and U.S. Pat. No. 7,893,101 disclose various solid forms comprising apremilast include single-component and multiple-component forms, including crystal forms and amorphous forms and their mixture comprising one or more of the Forms A, B, C, D, E, F, G and an amorphous solid form and provides representative XRPD patterns, DSC plots, TGA plots and DVS plots for each of Forms A, B, C, D, E, F and G.
WO 2014/072259 discloses pharmaceutical composition of amorphous apremilast with at least one excipients prepared by melt extrusion technique.
There is no disclosure found about the process for the preparation of an amorphous form of apremilast and its characterization as well as physiochemical properties and its stability.
The different physical properties exhibited by polymorphs affect important pharmaceutical parameters such as storage, stability, compressibility, density and dissolution rates (important in determining bioavailability). Stability differences may result from changes in chemical reactivity (e.g., differential hydrolysis or oxidation, such that a dosage form discolors more rapidly when comprised of one polymorph than when comprised of another polymorph), mechanical changes (e.g., tablets crumble on storage as a kinetically favored crystalline form converts to thermodynamically more stable crystalline form) or both (e.g., tablets of one polymorph are more susceptible to breakdown at high humidity).
An amorphous form generally provides better solubility and bioavailability than the crystalline form and may be useful for formulations which can have better stability, solubility and compressibility etc which are important for formulation and product manufacturing.
Therefore, it is desirable to have a stable amorphous form of drug with high purity to meet the needs of regulatory agencies and highly reproducible processes for its preparation.
In view of the above, it is therefore, desirable to provide an efficient, more economical, less hazardous and eco-friendly process for the preparation of amorphous form of apremilast. The amorphous form provided herein is stable under ordinary stability conditions with respect to purity and storage.